Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while ex
- PDF / 632,460 Bytes
- 9 Pages / 595.28 x 793.7 pts Page_size
- 88 Downloads / 139 Views
RESEARCH
Open Access
Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while extracellular matrix metalloproteinase inducer indicates prognosis Anja Rabien1*, Carsten Stephan1,2, Ergin Kilic3, Wilko Weichert4, Glen Kristiansen5, Kurt Miller1, Klaus Jung1,2 and Andreas Erbersdobler6
Abstract Background: Matrix metalloproteinases can promote invasion and metastasis, which are very frequent in renal cell carcinoma even at the time of diagnosis. Knowing the reversion-inducing cysteine-rich protein with Kazal motifs (RECK) as an inhibitor of matrix metalloproteinases and the extracellular matrix metalloproteinase inducer (EMMPRIN) protein as inducer, we aimed to determine their expression, localization and possible antagonistic action in the pathogenesis and progression of renal cell tumors in a retrospective study. Methods: Tumor and adjacent normal tissues of 395 nephrectomized patients were immunostained for RECK and EMMPRIN on a tissue microarray. Results: RECK strongly decreased in renal cell carcinoma compared to normal counterparts (Wilcoxon signed rank test, P < 0.001), and it discriminated tumor entities showing the highest expression in oncocytomas. EMMPRIN, however, could be significantly correlated to pT stage and Fuhrman grading (Spearman’s correlation coefficient rs = 0.289 and rs = 0.382, respectively). Higher expression of EMMPRIN was associated with decreased overall survival in Kaplan-Meier analysis (P < 0.001), and the EMMPRIN level could independently predict survival for cases without metastasis and involvement of lymph nodes. Decreased RECK expression was confirmed by Western blotting in tissue of eight normal/tumor matches of patients after radical nephrectomy, whereas the EMMPRIN pattern appeared to be heterogeneous. Conclusions: We propose RECK down regulation in renal cell carcinoma to be an early event that facilitates tumor formation and progression. EMMPRIN, however, as a prognostic tumor marker, increases only when aggressiveness is proceeding and could add an additional step to invasive properties of renal cell carcinoma. Keywords: RECK, EMMPRIN, Renal cell carcinoma, TMA
Background Kidney cancer is not the most common malignancy, but with a five-year survival rate of 70% in the United States [1] the outcome is often poor. In renal cell carcinoma (RCC) which represent the majority of 85-90% of kidney neoplasms [2,3], survival is mostly determined by distal metastases detected in 30% of the patients even at the * Correspondence: [email protected] 1 Department of Urology, Research Division, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany Full list of author information is available at the end of the article
time of diagnosis [2]. Usually, RCC can be recognized by sonography, but as symptoms are lacking until late stages of the disease, metastasis of RCC is the main problem in therapeutic approaches [2,3]. Due to the resistance of RCC to radio- and chemotherapy, only surgery can be curative if
Data Loading...
